| Budget Amount *help |
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 2003: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥11,300,000 (Direct Cost: ¥11,300,000)
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| Research Abstract |
The governmental resource for medicare is about 3000 million yen per year in Japan. The population of ESRD is 200 thousand and the expense for each patient is 5 million yen per year. Thus 100 million yen is currently spent for ESRD in each year. Given the fact that the entry to ESRD is predominantly increasing from type 2 DM nephropathy, it is necessary to develop the therapeutic approach controlling the progressive renal disease.
In this project, the efficacy of endothelial transplantation to renal disease was firstly investigated. The thrombotic micro-angiopathy (TMA) was induced to athymic nude rats injecting anti glomerular endothelial antibody super selectively to renal artery. The endothelial injury is initiated immediately after the injection, while its recovery process partly starts 3-4 days later as the endothelial proliferation. Therefore, the supplementation of endothelial cells to the defective sites may increase the number of regenerating glomeruli, accelerate the recovery
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process, and preserve renal function. Three days after the initiation of TMA, human umbilical venous endothelial cells (HUVE) were arterially injected to animals via catheter thru left jugular artery. One week after the injection of HJVEC, blood sampling was performed and the intact kidney was removed. After 24 h, the increase of BUN was examined and found the statistically significant increase because of the TMA kidney. This increase was reduced when HUVEC was transplanted to TMAA kidney. When rat renal interlobular arterial endothelial cells were injected instead of HUVEC, this increase was further decreased. The injected cells were observed at glomerular tuft even one week after the transplantation. It was also confirmed by electron microscopy. The hemodynamic effect of endothelial transplantation was examined using intravital video CCD camera which efficiently elucidated the peritubular no flow phenomena in ischemia reperfusion injury (ref 12). The glomerular red blood cell flow, initially low flow, was increased several minutes after the endothelial transplantation. Therefore the efficacy of endothelial transplantation in TMA model is partly derived from the improvement of glomerular blood flow.
In parallel to these experiments, we developed green fluorescent rats to investigate the efficacy of bone marrow transplantation to several renal disease model, such as TMA, ischemic acute renal failure, chronic interstitial renal disease, SHC-renal failure, and crescentic glomerular nephritis. These projects are currently ongoing. During this project, at least one group reported the efficacy of bone marrow transplantation to ischemic acute renal failure though we could find deterioration during this short period. Therefore, the excretion factors from bone marrow cells were considered rather pivotal instead of transplanted bone marrow cells. Among the factors investigated, G-CSF is one of the promising factors related to stem cell transplantation, that was effective for the recovery process of ischemia-reperfusion injury, and that mechanism is currently investigating. In addition to these cell transplantation experiments, we elucidated the efficacy of hydroxyl radical scavenger to ischemia-reperfusion injury and got the acceptance of publication recently. This project was successfully conducted and generated valuable observations during the research periods. Less
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